Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

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Gewählte Publikation:

Heu, C.
Methotrexate concentrations in third space fluids in comparison with serum concentrations in patients with osteosarcoma
Humanmedizin; [ Diplomarbeit ] Medical University of Graz; 2014. pp. 82 [OPEN ACCESS]
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Autor*innen der Med Uni Graz:
Betreuer*innen:
Leithner Andreas
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Abstract:
Background: Besides surgery, high-dose Methotrexate is a mainstay of osteosarcoma treatment. However, it is associated with severe adverse effects, which are partly dose-dependent. Methotrexate is known to accumulate in tissues, cavities and so-called third spaces (periprosthetic seromas) leading to local toxicity and delayed elimination. To avoid this, considerable periprosthetic seromas are punctured in our department. We compared the concentrations of Methotrexate in serum and periprosthetic seromas to describe a potential toxic risk based on a third space effect. Methods: In 45 osteosarcoma patients who were treated with endoprosthesis and high-dose Methotrexate, we retrospectively analysed Methotrexate concentrations in periprosthetic seromas and serum. Differences were assessed by means of a Wilcoxon test. Results: 112 periprosthetic seroma punctures were performed in 18 of 45 patients. Methotrexate concentrations were determined in 61.1% of all punctures. At 24 hours the periprosthetic seroma concentrations were 1.49-42.97 (median 14.86, p=0.001) and at 48 hours 1.36-52.56 (median 8.50, p<0.001) higher than the corresponding serum levels. At 72 hours the periprosthetic seroma concentrations were in median 2.66 (p=0.015, range 0.66-5.82) times higher than the corresponding serum levels. At 24 hours, highly toxic concentrations were observed in seromas (median 109.83, range 4.91-170.71µmol/L). Conclusions: Methotrexate concentrations of periprosthetic seromas are significantly higher than corresponding serum levels possibly contributing to a third space effect. To avoid severe adverse effects puncture of these effusions should be considered.

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